The objective of this program is to provide efficient synthetic methods for the synthesis of steroid- and terpenoid-like molecules of medicinal and biological interest. This effort will result in the preparation of fusidic acid and several structural analogs that are not available by partial synthesis from existing steroid or terpenoid precursors. Two recently devised, efficient schemes for the homoannelation and alkylation of alpha- methylene ketones will be exploited to prepare tetracyclic systems which are of use as intermediates for these syntheses. Use will be made of a method devised during the previous grant period for the formation of the synthetically demanding and strained trans-syn-trans backbone. Two potentially efficient means for the addition of the characteristic fusidic acid side chain are currently being explored on model systems under the present award and will be supplied to the tetracyclic intermediates proposed in this application. Through these syntheses, molecules related to the antibiotic fusidic acid that may be more therapeutically specific than the naturally occurring steroids and terpenoids will be prepared, and their pharmcological activity evaluated.